gimeracil and eniluracil

Colorectal carcinoma is an important cause of cancer morbidity and mortality. 5-fluorouracil has been the major chemotherapeutic agent for the treatment of colorectal carcinoma for the past four decades. This regimen is noncurative, and its impact on survival is unclear. Attempts at identifying more effective chemotherapeutic agents for colorectal cancer have yielded oral formulations and prodrugs of 5-fluorouracil with apparently equivalent efficacy. Specific thymidylate synthase inhibitors are now available. Platinum analogues with activity in colorectal carcinoma, and no cross-resistance to the antimetabolites have also been developed. The topoisomerase I inhibitors represent a new class of agents with a novel mechanism of action. These agents are in phase II and Phase III clinical trials, others have been approved for clinical use within the last 3 years.

Topics: Antineoplastic Agents; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Fluorouracil; Glutamates; Guanine; Humans; Pemetrexed; Platinum Compounds; Pyridines; Quinazolines; Tegafur; Thiophenes; Uracil

5-Fluorouracil (5-FU) has been the mainstay of systemic therapy for colorectal cancer since its initial development 40 years ago. Efforts to improve the therapeutic index of 5-FU have included alteration of schedule and addition of biochemical modulators. An understanding of 5-FU mechanisms of action has resulted in major therapeutic advances in the past 10 years; however, a plateau has been reached in the efficacy of 5-FU, mandating a paradigm shift for those involved in colorectal cancer drug development. One direction vigorously pursued is the development of orally administered fluoropyrimidines that maintain or improve upon the effectiveness of intravenous 5-FU. In this paper the preclinical and clinical development of oral fluoropyrimidines and their modulators is reviewed, including UFT, capecitabine, ethynyluracil and S-1.

Topics: Administration, Oral; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Enzyme Inhibitors; Fluorouracil; Humans; Oxidoreductases; Pyridines; Tegafur; Uracil